Objectives: (1) To elucidate the pathways of biosynthesis and metabolism of glycolipids and other lipids in the nervous system, both in vitro and in vivo; (2) to determine the turn-over rates of these lipids in vivo, their functions, and control mechanisms; (3) to examine, in particular, the synaptic region to find the functional roles of the various lipids in nerve impulse transmission; and finally, (4) to relate these results to normal and pathological chemistry and activities of the brain. (5) Following the discovery of a new myelin protein (DM-20), the turn-over of the protein components of myelin, myelin development, and the specific nature of the lipid-protein complex of myelin is being examined. It is hoped that this research will elucidate the metabolic pathways concerned with glycolipids such as the cerebrosides and gangliosides. It is planned to isolate and characterize the individual enzyme activities. These in vitro studies will be related to in vivo experiments in which interrelationships and turn-over rates of the lipids have been studied. While much of this work has involved brain tissue, a recent approach has been made on erythrocyte glycolipids. Since certain pathological conditions involve glycolipids, e.g. Gaucher's Tay-Sachs', metachromatic leudosystrophy, etc., these studies should aid in the understanding of the metabolic lesions. The blood studies may provide a convenient tool for studying some of these lipidoses in humans during life. Several aspects of this research project, i.e. subcellular distribution of the glycolipids and the properties of glycolipids as constituents of lipid-bilayer membranes, are directly related to function. It is thought that these studies will help to elucidate the biological role of the glycolipids in cells.